The invention relates to a method for risk stratification for acute coronary syndrome (ACS), in particular acute myocardial infarction (AMI) and angina pectoris (AP), wherein provasopressin (proAVP) or fragments and partial peptides thereof, in particular copeptin or neurophysin II, is determined by an in vitro diagnosis. The invention further relates to suitable combinations of biomarkers for in vitro diagnostics.
Risk stratification is becoming increasingly important for cardiac disease in symptomatic as well as asymptomatic patients. In particular for acute coronary syndrome there is a great need for suitable risk stratification.
Risk stratification is used to identify patients with an unfavorable prognosis, for intensive diagnostics, and for therapy/treatment, with the objective of enabling an optimal clinical outcome. Accordingly, the aim of suitable risk stratification is to follow effective treatment methods for acute coronary syndrome, using percutaneous coronary intervention and the newest medicaments.
Appropriate treatment requires early diagnosis and differentiation of acute coronary syndrome, even upon emergency room admission, in conjunction with clinical decisions. Due to nonspecific symptoms such as chest pain in acute coronary syndrome, the differentiation and delineation from other diseases as well as the identification of acute coronary syndrome are essential.
In the prior art, the use of biochemical markers, in particular classical markers such as cardiac troponin, myoglobin, and CK-MB mass, has been attempted for prognosis of myocardial infarction (Katus, H. A.; Remppis, A.; Scheffold, T.; Diederich, K. W., and Kuebler, W. (1991): Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction, Am J Cardiol 67 (16): 1360-1367). Type B natriuretic peptide (BNP) together with pro-BNP (NT-ProBNP) (EP 1363128 B1, EP 1666881 A2) has proven to be another effective biochemical marker in myocardial diagnostics.
Copeptin (also referred to as C-terminal proAVP) has been described in WO 2006/018315 (BRAHMS AG) as a biomarker for in vitro diagnosis of AMI. A corresponding copeptin assay is disclosed in Morgenthaler et al. (Nils G. Morgenthaler, Joachim Struck, Christine Alonso, and Andreas Bergmann, Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin, Clinical Chemistry 52: 112-119, 2006).
Neurophysin has been described as a marker for nicotine uptake (Robinson A. G., Isolation, assay, and secretion of individual human neurophysins, J Clin Invest 1975; 55: 360-367), malignancy- and nonmalignancy-related syndrome of inappropriate ADH secretion (SIADH), and nephrogenic diabetes insipidus (Pullan P. T., Clappison B. H., Johnston C. I., Plasma vasopressin and human neurophysins in physiological and pathological states associated with changes in vasopressin secretion, J Clin Endocrinol Metab 1979; 49: 580-587; North W. G., LaRochelle F. T., Jr., Melton J., Mills R. C., Isolation and partial characterization of two human neurophysins: their use in the development of specific radioimmunoassays. J Clin Endocrinol Metab 1980; 51: 884-891).
However, a disadvantage of the known diagnostic methods using the markers known heretofore is that early and complete identification of at-risk patients is not achieved, and therefore risk stratification is inadequate. An object of the invention, therefore, is to develop a method for risk stratification for acute coronary syndrome which allows improved identification of at-risk patients.
A further disadvantage is that in the prior art, sufficient sensitivity and/or specificity of the markers is usually not achieved.
A further object, therefore, is to provide a method for risk stratification for acute coronary syndrome, wherein at least one marker or a combination of markers has sufficient sensitivity and specificity in an in vitro diagnosis.